Autosomal dominant condition of variable severity, characterised by a range of benign tumours in various organ systems of the body

Aetiology

• Autosomal dominant but new mutations common
  • Chromosomes 9q34 and 16p13.3
  • Caused by loss-of-function mutations in the Tuberous Sclerosis Complex 1 (TSC1) and Tuberous Sclerosis Complex 2 (TSC2) tumour suppressor genes
  • Code for tuberin and hamartin
  • Tumour regulating genes are in the same pathway
• These mutations lead to hamartoma formation across various body systems
• Penetrance is variable (but high)
• Disease expression is variable - different people affected differently, even in the same family

Clinical presentation

Skin manifestations

• Angiofibromas: dome-shaped, firm papules in a butterfly distribution across the face
• Ashleaf macules: oval patches of hypopigmented skin that fluoresce under a Wood's light
• Shagreen patch: leathery, cobbled plaque, often on the sacrum, that is dimpled like orange peel
• Ungal fibromas: smooth, fleshy tumours that grow from the nail folds either around or under the nail
• Café au lait patches: hyperpigmented macules on the bod

Neurological manifestations

• Epilepsy: the most common neurologic manifestation, often with onset in infancy or childhood
• Learning difficulties: cognitive impairments are common, with varying severity
• Behavioural abnormalities: this may include autistic features, ADHD-like symptoms, and other behavioural problems

Other manifestations

• Retinal hamartomas: these can lead to visual disturbances
• Cardiac rhabdomyomas: these are benign heart tumours and may cause cardiovascular complications